scholarly journals LIPOPOLYSACCHARIDE-INDUCED IMMUNOLOGICAL STRESS AT EARLY STAGES OF PREGNANCY AFFECTS THE DEVELOPMENT OF GONADOTROPIN RELEASING-HORMONE (GNRH)-PRODUCING SYSTEM

2019 ◽  
Vol 19 (1S) ◽  
pp. 24-26
Author(s):  
V M Ignatiuk ◽  
M S Izvolskaia

The aim of the present work was to study the development of afferent bonds between GnRH- and monoaminergic neurons in rat fetuses and to identify possible targets affected by LPS-induced inflammation. The innervation was analyzed using retrograde tracing method with DiI dye. At ED17 and ED21 olfactory bulbs (the area of GnRH migration) are innervated with monoaminergic neurons of septum and in lateral hypothalamus. The GnRH- and monoaminergic neuron interaction zones are sensitive to LPS (E. coli) prenatal exposure, which induces pro-inflammatory cytokine synthesis. We suppose that the olfactory bulbs of fetal forebrain can be a possible area of cytokine influence on GnRH- and monoaminergic neuron interaction.

2021 ◽  
Vol 22 (3) ◽  
pp. 1497
Author(s):  
Edina Pandur ◽  
Kitti Tamási ◽  
Ramóna Pap ◽  
Gergely Jánosa ◽  
Katalin Sipos

Macrophages are essential immune cells of the innate immune system. They participate in the development and regulation of inflammation. Macrophages play a fundamental role in fighting against bacterial infections by phagocytosis of bacteria, and they also have a specific role in immunomodulation by secreting pro-inflammatory cytokines. In bacterial infection, macrophages decrease the serum iron concentration by removing iron from the blood, acting as one of the most important regulatory cells of iron homeostasis. We examined whether the Gram-positive and Gram-negative cell wall components from various bacterial strains affect the cytokine production and iron transport, storage and utilization of THP-1 monocytes in different ways. We found that S. aureus lipoteichoic acid (LTA) was less effective in activating pro-inflammatory cytokine expression that may related to its effect on fractalkine production. LTA-treated cells increased iron uptake through divalent metal transporter-1, but did not elevate the expression of cytosolic and mitochondrial iron storage proteins, suggesting that the cells maintained iron efflux via the ferroportin iron exporter. E. coli and P. aeruginosa lipopolysaccharides (LPSs) acted similarly on THP-1 cells, but the rates of the alterations of the examined proteins were different. E. coli LPS was more effective in increasing the pro-inflammatory cytokine production, meanwhile it caused less dramatic alterations in iron metabolism. P. aeruginosa LPS-treated cells produced a smaller amount of pro-inflammatory cytokines, but caused remarkable elevation of both cytosolic and mitochondrial iron storage proteins and intracellular iron content compared to E. coli LPS. These results prove that LPS molecules from different bacterial sources alter diverse molecular mechanisms in macrophages that prepossess the outcome of the bacterial infection.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S145-S146
Author(s):  
E Marlina ◽  
B Hirani ◽  
V Mercadante ◽  
M Shephard ◽  
S Kishida ◽  
...  

Abstract Background Probiotics have previously showed evidence of being efficacious in inducing and maintaining remission in post-operative recurrent pouchitis. The potential mechanism of action of probiotics has been attributed to their ability to reduce pro-inflammatory cytokine production, both within the mucosal tissue and systemically. We present our study which characterises the anti-inflammatory effects of probiotics on the oral epithelium and in the treatment of oral lichen planus (OLP), a chronic inflammatory disease of the oral mucosa. Methods VSL#3 (VSL#3-ACTIVE batch 703093 Exp date 04/2019) is a highly concentrated (450 billion live bacteria per sachet) poly-probiotic food supplement that contains eight different strains of live bacteria. The mouth ordinary epithelium cell line (MOE-1a) was stimulated with VSL#3 plus or minus the pro-inflammatory bacteria E. coli. The resultant effects on cytokine production and wound healing were measured using ELISA and live cell imaging. Wound closure was calculated using ImageJ software. OLP patients (n = 80) and healthy controls (n = 44) were recruited from UCLH Eastman Dental Hospital (Ethics 17/LO/0475) and saliva and blood samples tested for CXCL10 levels using an ELISA. OLP patients with active disease (n = 30) were recruited into a double-blind placebo-controlled proof-of-concept trial investigating the potential benefit of VSL#3 in the treatment of clinical symptoms (NCT03052179). Patients consumed two sachets twice daily for 30 days with a 30-day follow-up. Clinical questionnaires, saliva and peripheral blood were collected on days 0, 30 and 60. A daily quality of life and compliance diary was used by all participants. Results The addition of VSL#3 to MOE1a cells stimulated with E. coli resulted in a significant reduction in pro-inflammatory cytokine secretion and an acceleration in wound healing. OLP patients were found to have an elevation in the pro-inflammatory chemokine CXCL10 both locally (saliva) and systemically (serum) compared with healthy controls. Finally, the clinical trial demonstrated that VSL#3 was tolerated and safe for patients with OLP. Although there is no statistical evidence, descriptive results suggest that VSL#3 can confer some beneficial effects on patients with active OLP. We noted a reduction in the number of sites of disease activity and an improvement in quality of life in the VSL#3 group compared with placebo. Corticosteroid usage was also reduced in the VSL#3 group. Conclusion VSL#3 has the ability to improve oral epithelial wound healing and reduce pro-inflammatory cytokines secretion in vitro. In OLP, the consumption of VSL#3 seems to provide some clinical benefits, but due to the study size a more substantial multi-centre trial is necessary to confirm these observations.


1997 ◽  
Vol 4 (3) ◽  
pp. 197-204 ◽  
Author(s):  
P. Villa ◽  
C. Meazza ◽  
M. Sironi ◽  
M. Bianchi ◽  
P. Ulrich ◽  
...  

1999 ◽  
Vol 67 (10) ◽  
pp. 5176-5185 ◽  
Author(s):  
Federica Ciacci-Woolwine ◽  
Patrick F. McDermott ◽  
Steven B. Mizel

ABSTRACT We have previously demonstrated that salmonellae, but notEscherichia coli or Yersinia enterocolitica, stimulates tumor necrosis factor alpha (TNFα) production in the human promonocytic cell line U38. Subsequent analysis revealed that the TNFα-inducing activity of salmonellae was associated with flagellin, a major component of flagella from gram-negative bacteria. In the present study, we have explored the basis for the apparent specificity of action of Salmonella flagella on TNFα expression in U38 cells and have extended this analysis to normal human peripheral blood mononuclear cells (PBMC). Flagella from the enteropathogenicE. coli strain E2348/69, Y. enterocoliticaJB580, and Pseudomonas aeruginosa PAO1, which did not induce significant levels of TNFα production in U38 cells, were as potent as Salmonella flagella in terms of TNFα and interleukin 1β activation in PBMC. However, TNFα production in U38 cells was greatly enhanced when these cells were stimulated with flagella from E. coli, Y. enterocolitica, andP. aeruginosa in the presence of a costimulant, phorbol 13-myristate acetate. These findings are consistent with the hypothesis that the activation or differentiation state of a monocyte may have a substantial effect on the cell’s responsiveness to flagellum stimulation of cytokine synthesis. Furthermore, these results indicate that cytokine induction in monocytes may be a general property of flagella from gram-negative bacteria.


1992 ◽  
Vol 41 (3) ◽  
pp. 235
Author(s):  
Toshikatsu Okumura ◽  
Akira Uehara ◽  
Shigeru Kitamori ◽  
Masayoshi Namiki

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3218-3218
Author(s):  
Thomas Luft ◽  
Andreas Wagner ◽  
Michael Conzelmann ◽  
Sascha Dietrich ◽  
Oliver Krämer ◽  
...  

Abstract Abstract 3218 Inhibition of JAK1 is an emerging clinical concept that has promise for a variety of autoimmune diseases, myeloproliferative diseases and post-transplant immunosuppression, but similarly raises concerns regarding immunosuppressive side effects. At the example of IL-12p70 production in human monocyte-derived dendritic cells we demonstrate that JAK1 has a dual role in differentially regulating effects of weak and strong activation stimuli. We have demonstrated recently that weak NF-kB-activating stimuli (e.g. CD40L or LPS) require complementary JAK1-targeting cytokines such as IFN-g to induce IL-12p70. This pathway involves RELA, CREL, JAK1 and/or JAK2, STAT1, IRF1 and IRF8 and is inhibited by RELB and TYK2 (Conzelmann et al. Biochem Pharm. 2010, 80(12):2074–86). Here we provide evidence for an alternative IL-12 stimulating pathway depending on strong NF-kB activating stimuli (e.g. intact E. coli or LPS plus IL-1b). siRNA silencing demonstrated that this pathway is specifically inhibited by JAK1 and the transcription factor STAT3, but is not influenced by any of the other JAK/STAT family members. Both IL-12p35 and p40 mRNA expression is directly inhibited by STAT3. Furthermore, ChIP-assays revealed that STAT3 binds directly to a combined STAT/NF-kB site at the IL-12p35 promoter without altering access of RELA and CREL. Extending the cytokine panel we found that E.coli-induced IL-6 and TNF-a production is similarly inhibited by the JAK1/STAT3 pathway whereas IL-10 expression is not affected. The observed dual effects of JAK1 are clearly confirmed by the JAK1/2 inhibitor INCB018424 (Ruxolitinib) which enhances E.coli-induced cytokines whilst strongly inhibiting cytokine production stimulated by CD40L/IFN-g. In summary, our study suggests that blockade of JAK1 specifically inhibits pro-inflammatory effects of weak, IFN-g dependent, NF-kB activating stimuli while enhancing inflammatory cytokine expression induced by strong activation stimuli. Inhibition of JAK1/2 by INCB018424 (Ruxolitinib) would therefore represent a novel immunosuppressive approach that may spare the immune defence against invading pathogens. Disclosures: No relevant conflicts of interest to declare.


2019 ◽  
Vol 123 (5) ◽  
pp. S62
Author(s):  
R. Khanferyan ◽  
L. Gevorkyan ◽  
L. DuBuske

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